RESUMO
Multiple sclerosis [MS] is a chronic disease of the central nervous system and one of the most common causes of neurological disability among those aged 20-40 years, particularly in women. Major histocompatibility complex [MHC] Class II genes are known to be involved in the development of MS. One of the important groups of this complex is the HSP gene family, especially HSP70, which is induced under stress conditions. The aim of the present case-control study was to determine the association between the heat shock protein 70 [HSP70] and risk of MS in Iranian patients by genotyping the rs1061581 gene polymorphism. A total of 50 relapsing-remitting MS [RRMS] patients and 50 healthy control subjects were considered for this study. Genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism [PCRRFLP] method. PCR-RFLP results of twenty-five randomly selected samples were confirmed by DNA sequencing. Genotypic and allelic distributions were compared between the case and control groups. We observed no significant difference in the distribution of rs1061581 genotype and allele frequencies between RRMS patients and controls. In addition, there was no association between the HSP70 gene polymorphism and the clinical variables in the case group. Our data indicate that HSP70, in particular rs1061581, is unlikely to be involved in the susceptibility to or the severity of RRMS in Iranian patients. Further large prospective studies are required to confirm these findings
RESUMO
Background: Multiple sclerosis [MS] is the most common autoimmune disease of the central nervous system [CNS]. The main cause of the MS is yet to be revealed, but the most probable theory is based on the molecular mimicry that concludes some infections in the activation of T cells against brain auto-antigens that initiate the disease cascade
Objectives: The Purpose of this research is the prediction of the auto-antigen potency of the myelin proteolipid protein [PLP] in multiple sclerosis
Materials and Methods: As there wasn't any tertiary structure of PLP available in the Protein Data Bank [PDB] and in order to characterize the structural properties of the protein, we modeled this protein using prediction servers. Meta prediction method, as a new perspective in silico, was performed to find PLPs epitopes. For this purpose, several T cell epitope prediction web servers were used to predict PLPs epitopes against Human Leukocyte Antigens [HLA]. The overlap regions, as were predicted by most web servers were selected as immunogenic epitopes and were subjected to the BLASTP against microorganisms
Results: Three common regions, AA[58-74], AA[161-177], and AA[238-254] were detected as immunodominant regions through meta-prediction. Investigating peptides with more than 50% similarity to that of candidate epitope AA[58-74] in bacteria showed a similar peptide in bacteria [mainly consistent with that of clostridium and mycobacterium] and spike protein of Alphacoronavirus 1, Canine coronavirus, and Feline coronavirus. These results suggest that cross reaction of the immune system to PLP may have originated from a bacteria or viral infection, and therefore molecular mimicry might have an important role in the progression of MS
Conclusions: Through reliable and accurate prediction of the consensus epitopes, it is not necessary to synthesize all PLP fragments and examine their immunogenicity experimentally [in vitro]. In this study, the best encephalitogenic antigens were predicted based on bioinformatics tools that may provide reliable results for researches in a shorter time and at a lower cost
Assuntos
Humanos , Epitopos , Simulação por Computador , Pesquisa , Proteína Proteolipídica de Mielina , Antígenos HLARESUMO
Hepatitis C virus [HCV] infection has been associated with a plethora of immune and autoimmune perturbations. A variety of conditions ranging from endocrinopathies to different skin diseases has been described in HCV infection. The aim of this study was to investigate the prevalence and clinical significance of HCV infection in patients with graves' disease [GD]. A total of 55 patients with GD [30 women, 25 men, mean age: 35.24 +/- 12.27 years] and 50 control subjects [28 women, 22 men, mean age: 33.34 +/- 11.99 years] were examined. Third generation ELISA test was used for detection of antibodies to HCV in human sera, and anti-HCV seropositivity was confirmed by recombinant immunoblot assay [RIBA]. All normal controls were anti-HCV negative whereas anti-HCV antibody was present in 1 patient with GD and confirmed by Western blotting. These results indicate that there was no significant difference of anti-HCV antibodies between patients and controls. In this study no relationship was found between GD and HCV infection, which imply that hepatitis C virus has not a direct causal role in the pathogenesis of GD, however, this does not rule out a hit and run virus induced disease